Porcine reproductive and respiratory syndrome virus (PRRSV) is a member of the family Arteriviridae in the order Nidovirales (Cavanagh et al., Virol., 176, 306–307 (1990)) that causes reproductive failure in breeding swine and respiratory problems in young pigs (see Rossow, Vet. Pathol., 35, 1–20 (1998)). The syndrome was first recognized as a “mystery swine disease” in the United States in 1987 and was discovered in Europe in 1990. A strain of PRRSV that is prevalent in Europe has been isolated and is referred to as the Lelystad virus (Wensvoort et al., Vet. Q., 13, 121–130(1991)). A North American PRRSV, referred to as VR-2332, has been isolated (Collins et al., J. Vet. Diagn. Investig., 4, 117–126 (1992)). The disease has also been referred to as Wabash syndrome, mystery pig disease, porcine reproductive and respiratory syndrome, swine plague, porcine epidemic abortion and respiratory syndrome, blue abortion disease, blue ear disease, abortus blau, and seuchenhafter spatabort der schweine. The disease is characterized by reproductive failure in pregnant sows and respiratory problems in pigs of all ages. The disease has a significant negative impact on the swine industry.
PRRSV is an enveloped positive single-stranded RNA virus. The 5′-capped and 3′-polyadenylated RNA of the virus is polycistronic, containing (5′ to 3′) two large replicase open reading frames (ORFs), 1a and 1b, and several smaller ORFs. In the infected cell, arteriviruses produce a nested set of six to eight major coterminal subgenomic mRNAs (sgmRNAs) each thought to express only the relative 5′-terminal ORF. These sgmRNAs have a leader sequence derived from the 5′ end of the genome that is joined at specific leader-body junction sites located downstream by an unclear discontinuous transcription mechanism (Lai, Adv. Exp. Med. Biol., 380, 463–471 (1995)). The sgmRNAs of PRRSV encode four glycoproteins (GP2 to 5, encoded by sgmRNAs 2 to 5), an unglycosylated membrane protein (M, encoded by sgmRNA 6), and a nucleocapsid protein (N, encoded by sgmRNA 7). The European prototype strain of PRRSV, Lelystad, contains all six of these proteins in the virus particle, but only the proteins encoded by ORFs 5 to 7 have conclusively been demonstrated to be in the virion of North American isolates.
Nucleotide and amino acid sequence comparisons of the 3′-terminal ORFs 2 to 7 have shown that there are significant differences between PRRSV strains native to Europe and those found in North America (Kapur et al., J. Gen. Virol., 77, 1271–1276 (1996), Murtaugh et al., Arch. Virol., 40, 1451–1460 (1995)). Substantial variation also occurs among North American PRRSV isolates. Genotypic comparison between strains VR-2332 and Lelystad has revealed that ORF 1a of VR-2332 is vastly different from that of Lelystad in both length and sequence, while ORF 1b is relatively conserved between the two strains of PRRSV. The 5′ leader sequence of VR-2332 was 31 bases shorter than that of Lelystad and differed considerably in nucleotide sequence. Regional amino acid sequence comparisons also revealed that although the recognized functional domains of the ORF 1a proteins were present in both strains, the proteins were not well conserved between these domains. Thus, although these two PRRSV strains cause similar diseases, they are different in the genes encoding structural proteins.
PRRSV continues to cause significant economic losses throughout the world. Vaccines are available, but they are based on one PRRSV strain, and there is evidence that PRRSV strains vary at the antigenic and genetic levels. In addition, since the virus was identified in Europe and in the United States, new disease phenotypes have continued to emerge.